Nasal Fentanyl and Buccal Midazolam for Dying Patients

NCT02009306 | Completed Phase 4 DMC

• 1 other identifier: PecEp1
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

When patients are dying they become unable to take oral medication and if they develop symptoms (e.g. pain or agitation) they need to be given a subcutaneous injection of medication. If they are at home this requires that a District Nurse is called and it can take a long time (sometimes hours) for the Nurse to arrive. This can be a very stressful time for the patient and family. There are 2 drug preparations which could potentially be given by family members in the home: Nasal fentanyl (PecFent) Buccal midazolam (Epistatus) If these preparations helped symptoms this would give much quicker symptom control for patients and might mean the District Nurse visit was not needed. In advance of a community based randomised trial of these modes of administration, it is important to assess the feasibility of such an approach in terms of carer acceptability and patient tolerability as well as determine appropriate sample sizes and sampling methods. There are 2 work packages which would help assess feasibility of a community trial:

1. 1.An open label randomised controlled trial comparing the use of PecFent with or without Epistatus versus standard subcutaneous breakthrough medication for the management of breakthrough pain (with or without agitation) in dying hospice patients who either remain in the hospice or go home.
2. 2.A qualitative interview study to capture the thoughts of relatives of these patients about the use of these preparations.

Conditions

Terminal Cancer

Keywords

Palliative; Symptom control; Hospice; Opioid; Benzodiazepine

Outcome Measures

Primary Outcomes (1)

• Time to adequate symptom control ('comfortable') from need for breakthrough medication (in minutes) according to patient (where possible), relatives and staff.

  Data will be captured by patient and/or carer and/or staff with regard to time from need for breakthrough medication (recognition of symptom) to adequate symptom control ('comfortable').

  30 minutes

Secondary Outcomes (6)

• Time (in minutes) from need for breakthrough medication (recognition of symptom) to administration of drug.

  30 minutes

• Need for additional oral or subcutaneous medication

  30 minutes

• Time (in minutes) to recurrence of symptoms according to patient (where possible), relatives and staff

  4 hours

• Patient comfort as measured by the modified Palliative care Outcome Scale Symptom list (POS-S) (patient /carer/ staff versions)

  30 minutes

• Visual analogue scales for pain and agitation completed by patient (where possible), relatives and staff at baseline (Time 0), 5, 10, 15, 20, 25 and 30 minutes for 1 breakthrough episode per day

  30 minutes

Study Arms (3)

PecFent and Epistatus

EXPERIMENTAL

Medication administered by family / carer for symptoms

Drug: PecFent and Epistatus; Drug: Standard subcutaneous medication

Standard subcutaneous medication

ACTIVE COMPARATOR

Standard subcutaneous medication - diamophine and / or midazolam administered by nursing staff

Drug: Standard subcutaneous medication

Epistatus Alone

EXPERIMENTAL

From 28/11/17 following approval from sponsor, ethics committee and MHRA a 3rd observational arm was introduced: Epistatus administered PRN by family / carer for symptoms

Drug: Standard subcutaneous medication; Drug: Epistatus Alone

Interventions

PecFent and Epistatus DRUG

PecFent will be supplied by Archimedes Pharma as two strengths of nasal spray solution at 1000 or 4000 mcg/mL fentanyl (as citrate). One spray contains 100 mcg or 400 mcg fentanyl (as citrate). Each bottle contains 1.55 ml ensuring delivery of 8 sprays of 100 or 400 mcg fentanyl (as citrate). PecFent is a commercially available product and packaging will be in accordance with the manufacturing authorisations (EU/1/10/644/001, EU/1/10/644/002, EU/1/10/644/005, EU/1/10/644/003, EU/1/10/644/004, EU/1/10/644/006). Epistatus will be supplied by Special Products Ltd. as buccal solution, packed in bottles containing solution for up to 4 x 1 ml doses, as per "Specials" licence. A pack also includes 4 x oral syringes used to administer the solution to the buccal cavity on either side of the mouth.

Also known as: Fentanyl and Midazolam

PecFent and Epistatus

Standard subcutaneous medication DRUG

Subcutaneous as needed medication will include: * Opioids for pain or dyspnoea * Diamorphine * Oxycodone * Fentanyl * Benzodiazepine and / or anti-psychotic for agitation * Midazolam * Levomepromazine * Haloperidol Anti-emetic for nausea * Cyclizine * Metoclopramide * Haloperidol * Levomepromazine * Anti-secretory drug for respiratory secretions * Glycopyrronium * Hyoscine butylbromide * Hyoscine hydrobromide

Also known as: Subcutaneous opioids and midazolam

Epistatus Alone; PecFent and Epistatus; Standard subcutaneous medication

Epistatus Alone DRUG

Epistatus will be supplied by Special Products Ltd. as buccal solution, packed in bottles containing solution for up to 4 x 1 ml doses, as per "Specials" licence. A pack also includes 4 x oral syringes used to administer the solution to the buccal cavity on either side of the mouth.

Also known as: Midazolam

Epistatus Alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult hospice in-patients fitting the following criteria will be approached to see if they are willing to participate in the study:
• diagnosis of terminal cancer and thought to have an estimated prognosis of between 1 and 2 weeks
• have capacity to consent to participation
• patients who, in the last 24 hours, have experienced at least one episode of breakthrough pain FOR ARMS 1 OR 2 (RCT) For Arm 3 must have had 1 episode of agitation necessitating the use of a benzodiazepine in the last 24 hours
• taking 60mg or more of oral morphine (or its equivalent) per 24 hours FOR ARMS 1 OR 2 (RCT) IF taking less than this dose of opioid could be enrolled in Arm 3 (Epistatus alone - change in protocol implemented 28/11/17
• have carers or family members who would be: willing to give the study medication to the patient likely to be at the hospice at least 50% of the time so that they are likely to be present to administer medication.

You may not qualify if:

• patients / carers / family members who in the opinion of the clinical team would be too distressed by the idea of participation
• patients with disease of the nasal/buccal mucosa preventing effective absorption of medication
• families who are unable to administer breakthrough medication e.g. problems with dexterity
• history of substance abuse - patient or carer / family.
• people who who might not adequately understand verbal explanations or written information given in English. The pilot is only recruiting 20 patients and Gloucestershire has a only a very small percentage of people who are not English speaking. It has been decided that it is not cost effective to fund translation for this pilot although this information will have to be taken into account when planning a larger study. We will capture information on the numbers of patients that may have been excluded and the languages that might have been needed.
• Participated in a medicinal trial within the last four months following the guidance from the Association of the British Pharmaceutical Industry.

Sponsors & Collaborators

• Gloucestershire Hospitals NHS Foundation Trust: lead

Study Sites (1)

Sue Ryder Leckhampton Court Hospice

Cheltenham, Gloucestershire, GL53 0QJ, United Kingdom

Location

Related Publications (1)

• Perkins P, Parkinson A, Akyea RK, Husbands E. Nasal fentanyl alone plus buccal midazolam: an open-label, randomised, controlled feasibility study in the dying. BMJ Support Palliat Care. 2020 Sep;10(3):300-303. doi: 10.1136/bmjspcare-2019-002029. Epub 2020 May 6.

  PMID: 32376759 DERIVED

MeSH Terms

Interventions

Fentanyl; Midazolam

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Paul Perkins, MB BCh FRCP (UK)

  Gloucestershire Hospitals NHS Foundation Trust and

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant in Palliative Medicine

Study Record Dates

• First Submitted: November 18, 2013
• First Posted: December 11, 2013
• Study Start: January 23, 2017
• Primary Completion: February 28, 2018
• Study Completion: February 28, 2018
• Last Updated: May 9, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)